Interrelation between tumor cell proliferation and 17-fluoresceinated estrone binding following primary tumor removal, radiation, cyclophosphamide, or tamoxifen

Abstract

The proportion of single intact viable mouse mammary tumor cells containing estrogen receptor (ER) as determined by 17-fluoresceinated estrone binding and the proportion labeled with [3H]thymidine (LI) have been assessed in the same cell population after either primary tumor removal, radiation, cyclophosphamide, or tamoxifen administration. Subsequent to tumor removal, the increase in LI occurring in a cell population from a residual tumor focus was associated with a concomitant decrease in the proportion of cells demonstrating 17-fluoresceinated estrone binding (fluorescence). As the level of LI in the tumor focus returned to that observed prior to tumor removal, the proportion of ER-containing cells simultaneously reverted to its original value. Following cyclophosphamide administration, there was a decrease in tumor LI and a concomitant elevation in the proportion of fluorescent cells which were dose related. The prolonged depression in LI following radiation was accompanied by a sustained increase in the proportion of ER-containing cells. Thus, the change in ER-containing cells was related to the alteration of the proliferating cell population by the various therapies. The findings support the thesis that fewer cells in the growth fraction of the tumor studied contain ER than in the nonproliferating cell pool. Following tamoxifen administration, a decrease occurred in the proportion of fluorescing cells due to competitive binding. There was no alteration in LI. This observation is not in conflict with the thesis that there is a correlation between ER and LI since the mechanism for reduction in detectable ER is different. These studies provide additional support to the credibility of the use of 17-fluoresceinated estrone binding for the determination of ER in individual tumor cells. They also indicate the usefulness of the method for obtaining biological information regarding tumor ER which cannot be obtained with the use of conventional biochemical analyses.